OPTiM Follow-up Shows Improved CR Rate With T-VEC in Melanoma

“A retrospective analysis of the phase III OPTiM study found that treatment with talimogene laherparepvec (T-VEC; Imlygic) resulted in complete responses (CR) in 17% of patients seen in all stages of melanoma. Median time to achieve a CR was 8.6 (6.0–13.6) months. A high proportion of response occurred in patients with early-stage disease and lower tumor burden, according to study authors.

“In OPTiM, a phase III trial in 436 patients with unresected stage IIIB to IV melanoma, T-VEC improved durable response rates from 2.1% to 16.3% versus subcutaneous GM-CSF. Overall response rates (ORR) for T-VEC and GM-CSF were 26.4% and 5.7%, respectively. Median overall survival (OS) was 23.3 months with T-VEC and 18.9 months with GM-CSF (HR, 0.79; 95% CI, 0.62–1.00; P = .051).”


Amgen Receives CHMP Positive Opinion For IMLYGIC™ (Talimogene Laherparepvec)

“Amgen AMGN, +1.94% today announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion recommending that IMLYGIC™ (talimogene laherparepvec) be granted approval for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (Stage IIIB, IIIC and IVM1a) with no bone, brain, lung or other visceral disease. If approved by the European Commission, IMLYGIC would be the first in a class of novel agents known as oncolytic immunotherapies.

“IMLYGIC, administered via intralesional injection, is designed to cause the death of tumor cells and to initiate an anti-tumor immune response.”


T-VEC/Pembrolizumab Combination Demonstrates Safety in Melanoma

“The combination of the attenuated oncolytic virus talimogene laherparepvec (T-VEC) and the immune checkpoint inhibitor pembrolizumab has passed an early safety evaluation for unresectable melanoma, investigators reported at the 2015 European Cancer Congress (ECC).

“Treatment-related grade 3 adverse events occurred infrequently in a small phase Ib trial of combination therapy with T-VEC and pembrolizumab. No patient discontinued treatment because of adverse events and no treatment-related deaths occurred.

“ ‘T-VEC plus pembrolizumab was well tolerated, and we observed no dose-limiting toxicity,’ said Georgina V. Long, BSc, PhD, MBBS, associate professor at the University of Sydney in Australia. ‘Treatment-related adverse events were mostly grade 1/2. The combination of T-VEC and pembrolizumab is feasible and warrants further investigation.’ “


World First as Viral Immunotherapy for Skin Cancer Shows Patient Benefit in Phase III Trial

“A genetically engineered herpes virus can halt the progression of skin cancer by killing cancer cells and sparking the immune system into action against tumours, a landmark clinical trial has shown.

“It is the first time that a phase III trial of viral immunotherapy has definitively shown benefit for patients with cancer.

“The trial was led in the UK by researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and involved 64 research centres worldwide including the University of Oxford.

“Researchers randomised 436 patients with aggressive, inoperable malignant melanoma to receive either an injection of the viral therapy, called Talimogene Laherparepvec, or a control immunotherapy.”


FDA Panel Supports Approval of T-VEC

“Two days after the U.S. Food & Drug Administration signaled it might quash Amgen Inc.’s attempt to usher in a whole new class of virus-based cancer drugs, an advisory panel for the agency voted ‘yes’ on the question of whether the company’s experimental melanoma treatment, talimogene laherparepvec (T-VEC), has a favorable enough risk-benefit profile for approval. T-VEC is made from a modified herpes bug and would likely be the first among a number of virus-based cancer treatments in the pharma pipeline to be approved. Of the 23 members on the panel, all but one voted in favor of approval. The FDA doesn’t have to follow the direction of its advisory panels but it usually does.

“T-VEC, which is injected directly into melanoma tumors, is a version of herpes simplex virus that has been genetically modified so it only replicates in cancer cells, destroying tumors while sparing healthy tissues. It also includes a gene that encodes a type of cytokine, or protein, called granulocyte-macrophage colony-stimulating factor (GM-CSF), which recruits immune-boosting cells to the tumor. The hope is that the combination of the virus with GM-CSF will not only speed up the drug’s cancer-killing effect, but also stimulate the immune system to continue killing melanoma cells—even those that have traveled away from the treated tumor.

“In 2011, when T-VEC was in the early stages of development, Amgen paid a remarkable $425 million plus $575 million in milestone commitments to acquire its inventor, Biovex. At the time, there were a few hopeful signs: The FDA had granted the drug “fast-track” designation, indicating the potential to speed up its path to market. Then the agency added orphan designation for T-VEC, which could offer benefits such as tax credits and a period of market exclusivity if the drug is approved.”


FDA Advisory Committees Consider T-VEC for Metastatic Melanoma

“Two FDA advisory committees convened today to review Amgen’s biologic license application for its oncolytic virus, talimogene laherparepvec, as a treatment for metastatic melanoma.

“In a preliminary document released Monday, FDA reviewers questioned the design and results of a key phase 3 trial designed to evaluate talimogene laherparepvec, commonly referred to as T-VEC. The reviewers concluded there was not enough evidence to suggest the agent improves OS for patients with metastatic melanoma.

“Amgen representatives, thus, adjusted their presentation of results of the phase 3 study to address many of the questions raised in the FDA review.

“Members of the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee and its Oncologic Drugs Advisory Committee are expected to vote this afternoon about whether to recommend approval of T-VEC for this indication. Although the FDA is not required to follow the recommendations of its advisory committees, it often does.”


T-VEC plus Ipilimumab Appears Safe, Effective for Unresected Melanoma

“Talimogene laherparepvec combined with ipilimumab demonstrated tolerability at the planned doses without dose-limiting toxicities in patients with unresected, stage IIIB to IV melanoma, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting in New York.

“The combination also demonstrated higher overall and complete response rates than typical for either agent alone, results showed.

“Talimogene laherparepvec (T-VEC, Amgen) — a systemically active oncolytic immunotherapy derived from herpes simplex virus type 1 — yielded a higher durable response (≥ 6 months) than granulocyte-macrophage colony-stimulating factor (GM-CSF) in a phase 3 melanoma trial, according to study background.

“Igor Puzanov, MD, MSCI, FACP, of the division of hematology-oncology at Vanderbilt University Medical Center, and colleagues sought to evaluate the safety and efficacy of T-VEC in combination with ipilimumab (Yervoy, Bristol-Myers Squibb).”


T-VEC Extends OS in Patients with Unresected Stage III/IV Melanoma

“Patients with unresected stage IIIb, stage IIIc or stage IV melanoma treated with talimogene laherparepvec demonstrated a durable OS advantage compared with those who received granulocyte-macrophage colony–stimulating factor, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.

“Talimogene laherparepvec (T-VEC, Amgen) is a systemically active oncolytic immunotherapy derived from herpes simplex virus type-1. Upon injection directly into tumor tissue, T-VEC selectively infects and replicates in tumor cells. The virus replication leads to tumor cell lysis and exposure of tumor-specific antigens to the immune system, resulting in a local and systemic immune activation and an immune-mediated destruction of tumor cells throughout the body.

“T-VEC also is engineered to produce GM-CSF to enhance the local and systemic antitumor immune response, according to study background.”


FDA to Review Treatment Injected into Metastatic Melanoma Tumors

The gist: A treatment for metastatic melanoma called talimogene laherparepvec (T-VEC) will soon be reviewed by the FDA for treating patients with metastatic melanoma. If T-VEC is approved, doctors in the U.S. will be free to prescribe it to their patients. T-VEC is an immune system-boosting treatment that is injected directly into melanoma tumors. Learn more about it in this Need to Know blog post.

“Amgen (NASDAQ: AMGN) announced today that the Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) and the Oncologic Drugs Advisory Committee (ODAC) of the U.S. Food and Drug Administration (FDA) will jointly review the Company’s Biologics License Application (BLA) for talimogene laherparepvec. The FDA is currently reviewing the talimogene laherparepvec BLA for the treatment of patients with injectable regionally or distantly metastatic melanoma. The advisory committees will review talimogene laherparepvec at a meeting on April 29, 2015.

” ‘The incidence of melanoma has continued to rise in recent years, and even with recent additional options in treatment, there is an important unmet medical need,’ said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. ‘We look forward to discussing the efficacy and safety profile of talimogene laherparepvec with the advisory committees, and we are committed to working closely with the FDA during its review of the BLA.’ “